Pure populations of tumor cells are essential for the identification of tumor-associated proteins for the development of targeted therapy. In recent years, laser capture microdissection (LCM) has been used successfully to obtain distinct populations of cells for subsequent molecular analysis. The polycomb group (PcG) protein, enhancer of zeste homolog 2 (EzH2), a methyl-transferase that plays a key role in -transcriptional gene repression, is frequently overexpressed in several malignant tumors. High levels of EzH2 are often associated with advanced disease stage in many solid tumors; however, its role in the pathogenesis of pancreatic ductal adeno-carcinoma (PDAC) is poorly understood. Because of the limited sample availability and the absence of in vitro amplification steps for proteins, the use of LCM for proteomics studies largely depends on highly sensitive protein detection methods. Here, we developed a faster and sensitive Western blot protocol and validated it for the detection of EzH2 in ∼2,000 cells. Initially, cultured PANC-1 cells were used to optimize protein electrophoresis and western blotting conditions. Gradient gel electrophoresis in combination with optimized antibody concentrations, and a sensitive chemiluminescent assay provided a strong signal. In order to further confirm the role of EzH2 in PDAC, employing siRNA-mediated gene silencing via long lasting plasmid vectors containing shRNA, we investigated the potential role of EzH2 gene silencing in pancreatic cancer regression. Positive correlation of EzH2 expression was observed with advanced stage, serous histology, and increasing grade in pancreatic cancer patient tissues. Further EzH2 knockdown resulted in decreased cell growth and invasiveness. The findings of this study emphasize that western blotting of a LCM-generated pure population of cancer cells may be a valuable technique for the study of tumor-specific proteins.

A prominent feature of most cancers including Barrett's adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evolving genomic changes and growth of BAC cells. We show that the expression of RAD51 is elevated in BAC cell lines and tissue specimens, relative to normal cells. HR activity is also elevated and significantly correlates with RAD51 expression in BAC cells. The suppression of RAD51 expression, by short hairpin RNA (shRNA) specifically targeting this gene, significantly prevented BAC cells from acquiring genomic changes to either copy number or heterozygosity (P<0.02) in several independent experiments employing single-nucleotide polymorphism arrays. The reduction in copy-number changes, following shRNA treatment, was confirmed by Comparative Genome Hybridization analyses of the same DNA samples. Moreover, the chromosomal distributions of mutations correlated strongly with frequencies and locations of Alu interspersed repetitive elements on individual chromosomes. We conclude that the hsRAD51 protein level is systematically elevated in BAC, contributes significantly to genomic evolution during serial propagation of these cells and correlates with disease progression. Alu sequences may serve as substrates for elevated HR during cell proliferation in vitro, as they have been reported to do during the evolution of species, and thus may provide additional targets for prevention or treatment of this disease.

Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.

Title

Sciatic Hernia: a Comprehensive Review of the World Literature (1900-2008).

Date

March 2010

Journal

American Journal of Surgery

Excerpt

Sciatic hernias are considered the rarest pelvic floor hernias, with a very limited number of published reports worldwide. The condition has received limited attention in the surgical literature.

Ovarian cancer is the leading cause of mortality from gynecological malignancies, often undetectable in early stages. The difficulty of detecting the disease in its early stages and the propensity of ovarian cancer cells to develop resistance to known chemotherapeutic treatments dramatically decreases the 5-year survival rate. Chemotherapy with paclitaxel after surgery increases median survival only by 2 to 3 years in stage IV disease highlights the need for more effective drugs. The human immunodeficiency virus (HIV) infection is characterized by increased risk of several solid tumors due to its inherent nature of weakening of immune system. Recent observations point to a lower incidence of some cancers in patients treated with protease inhibitor (PI) cocktail treatment known as HAART (Highly Active Anti-Retroviral Therapy).

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research

Excerpt

PURPOSE: The aims of this study were to investigate telomere function in normal and Barrett's esophageal adenocarcinoma (BEAC) cells purified by laser capture microdissection and to evaluate the effect of telomerase inhibition in cancer cells in vitro and in vivo. EXPERIMENTAL DESIGN: Epithelial cells were purified from surgically resected esophagi. Telomerase activity was measured by modified telomeric repeat amplification protocol and telomere length was determined by real-time PCR assay. To evaluate the effect of telomerase inhibition, adenocarcinoma cell lines were continuously treated with a specific telomerase inhibitor (GRN163L) and live cell number was determined weekly. Apoptosis was evaluated by Annexin labeling and senescence by beta-galactosidase staining. For in vivo studies, severe combined immunodeficient mice were s.c. inoculated with adenocarcinoma cells and following appearance of palpable tumors, injected i.p. with saline or GRN163L. RESULTS: Telomerase activity was significantly elevated whereas telomeres were shorter in BEAC cells relative to normal esophageal epithelial cells. The treatment of adenocarcinoma cells with telomerase inhibitor, GRN163L, led to loss of telomerase activity, reduction in telomere length, and growth arrest through induction of both the senescence and apoptosis. GRN163L-induced cell death could also be expedited by addition of the chemotherapeutic agents doxorubicin and ritonavir. Finally, the treatment with GRN163L led to a significant reduction in tumor volume in a subcutaneous tumor model. CONCLUSIONS: We show that telomerase activity is significantly elevated whereas telomeres are shorter in BEAC and suppression of telomerase inhibits proliferation of adenocarcinoma cells both in vitro and in vivo.

Title

Complications Are Increased with the Need for an Abdominal-assisted Kraske Procedure.

Date

April 2004

Journal

The American Surgeon

Excerpt

The Kraske procedure offers a sphincter-saving alternative for surgical correction of rectal disease. This study was performed to investigate the complication rate with the traditional (transsacral) Kraske procedure versus an abdominal-assisted Kraske approach (laparoscopic or open). We conducted a retrospective review of all patients undergoing the Kraske procedure at Harper University Hospital over a 10-year period. A total of 54 patients were identified. Indications for surgery included rectal carcinoma (43), large villous adenomas (6), and other (5). Average post-operative follow-up was 40 +/- 25 months (mean +/- SD). Complications included rectocutaneous fistulae (9), perineal infections (13), and incontinence (8). In patients requiring an abdominal-assisted approach for colorectal mobilization, the fistula rate was significantly higher (33% vs 3%; P = 0.007), as were the rates of perineal infections (33% vs 17%) and of initial incontinence (25% vs 7%). The laparoscopic-assisted approach significantly reduced the operating time (272 +/- 72 minutes) compared to the open-assisted approach (498 +/- 138 minutes) (P < 0.001). The traditional Kraske procedure can be utilized in a safe, effective manner for treatment of rectal disease. Knowledge of the increased rate of complications with the abdominal-assisted Kraske approach can guide the patient and physician considering sphincter salvage.

Title

High 2-deoxy-2-[18f]fluoro-d-glucose Accumulation in a Case of Retroperitoneal Fibrosis Following Resection of Carcinoid Tumor.

Date

October 2003

Journal

Molecular Imaging and Biology : Mib : the Official Publication of the Academy of Molecular Imaging

Excerpt

Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been shown to be a highly sensitive diagnostic tool to stage, restage, and monitor the progress of various neoplasms. A number of physiological and non-neoplastic conditions, however, also may be associated with focal accumulation of FDG and can cause false-positive results. This work reports a 52-year-old man who had marked FDG accumulation in carcinoid tumor of the distal ileum. The tumor was resected. A follow-up FDG-PET scan one and a half years later revealed intense FDG accumulation in the abdominal periaortic region, suggesting recurrent malignancy. Computerized tomography (CT) of the abdomen showed soft tissue mass surrounding the aorta. Fine-needle aspiration biopsy of the periaortic soft tissue confirmed benign retroperitoneal fibrosis. This case shows that retroperitoneal fibrosis can cause intense FDG accumulation giving false impression of malignancy. In interpretation of whole-body FDG-PET, various physiological and benign causes of FDG accumulation must be considered in order to avoid pitfalls. The authors have reviewed the literature and discussed association of carcinoid tumor and retroperitoneal fibrosis.

Title

The Extent of Cryosurgery Increases the Complication Rate After Hepatic Cryoablation.

Date

June 2003

Journal

The American Surgeon

Excerpt

Although there have been many reports on the use of cryosurgery to ablate hepatic malignancies none have specifically examined the relationship of complication rates to the extent of cryoablation. A retrospective review from January 1997 to May 2002 identified 98 patients treated with hepatic cryotherapy. The extent of the cryosurgery was determined by the total number of lesions (TNL) and total estimated area (TEA) of the lesions from preoperative evaluation by CT scan and intraoperative evaluation by ultrasound. The major complication rate was 11 per cent. The 30-day mortality was 0 per cent, but the late procedure-related mortality was 2 per cent. Increasing the extent of cryotherapy measured by intraoperative ultrasound demonstrated significant increases in the complication rate and length of stay (LOS). With cryoablation of TEA > or = 30 cm2 there was a significant increase in the overall complication rate (56% vs 23%; P = 0.003) and LOS (8.8 +/- 6.9 vs 6.1 +/- 4.2; P = 0.022) compared with TEA < 30 cm2. Performance of concurrent procedures also led to a significant increase in complications (69% vs 29%; P = 0.010) and LOS (8.6 +/- 6.8 vs 6.0 +/- 4.0; P = 0.019). Multivariate analysis, however, showed intraoperative TEA > or = 30 cm2 to be the most significant independent predictor of increased complications and prolonged LOS.

To determine the frequency of c-Kit staining in desmoids and optimize an assay for clinical use, we stained 19 desmoids from various sites at various dilutions with 2 commonly used rabbit polyclonal, anti-c-Kit antibodies (A4502, DAKO, Carpinteria, CA; C-19, Santa Cruz Biotechnology, Santa Cruz, CA), with and without heat-induced epitope retrieval (HIER) in citrate buffer. Approdpriate external and internal control samples were evaluated for each test condition. At dilutions of 1:50 both antibodies stained substantial numbers of desmoids: with/without HIER, A4502, 89%/63%; C-19, 37%/74%. The staining was cytoplasmic without cell membrane accentuation. However, background stromal staining and nonspecific staining of endothelium and smooth and striated muscle were problematic with both antibodies at 1:50. At higher dilutions, C-19 stained no desmoid; however, diminished staining of external and internal control samples made it unreliable. A4502 similarly stained many fewer desmoids at higher dilutions. However, it retained strong staining of both external and internal control samples and showed much less nonspecific staining. Best results were achieved at 1:250 without HIER; only weak focal staining was present in 1 desmoid. With a simple immunohistochemical method optimized for clinical use, desmoid can be regarded as a c-Kit-negative tumor.

Bispeptide nucleic acids (bis-PNAs; PNA clamps), PNA oligomers, and DNA oligonucleotides were evaluated as affinity purification reagents for subfemtomolar 16S ribosomal DNA (rDNA) and rRNA targets in soil, sediment, and industrial air filter nucleic acid extracts. Under low-salt hybridization conditions (10 mM NaPO(4), 5 mM disodium EDTA, and 0.025% sodium dodecyl sulfate [SDS]) a PNA clamp recovered significantly more target DNA than either PNA or DNA oligomers. The efficacy of PNA clamps and oligomers was generally enhanced in the presence of excess nontarget DNA and in a low-salt extraction-hybridization buffer. Under high-salt conditions (200 mM NaPO(4), 100 mM disodium EDTA, and 0.5% SDS), however, capture efficiencies with the DNA oligomer were significantly greater than with the PNA clamp and PNA oligomer. Recovery and detection efficiencies for target DNA concentrations of > or =100 pg were generally >20% but depended upon the specific probe, solution background, and salt condition. The DNA probe had a lower absolute detection limit of 100 fg of target (830 zM [1 zM = 10(-21) M]) in high-salt buffer. In the absence of exogenous DNA (e.g., soil background), neither the bis-PNA nor the PNA oligomer achieved the same absolute detection limit even under a more favorable low-salt hybridization condition. In the presence of a soil background, however, both PNA probes provided more sensitive absolute purification and detection (830 zM) than the DNA oligomer. In varied environmental samples, the rank order for capture probe performance in high-salt buffer was DNA > PNA > clamp. Recovery of 16S rRNA from environmental samples mirrored quantitative results for DNA target recovery, with the DNA oligomer generating more positive results than either the bis-PNA or PNA oligomer, but PNA probes provided a greater incidence of detection from environmental samples that also contained a higher concentration of nontarget DNA and RNA. Significant interactions between probe type and environmental sample indicate that the most efficacious capture system depends upon the particular sample type (and background nucleic acid concentration), target (DNA or RNA), and detection objective.

BACKGROUND: The management of rectal cancer has been changing to include more sphincter-sparing procedures. We report our initial experience with a new technique incorporating laparoscopy and a transsacral approach for low or midlevel rectal cancer. Here, we tried to determine whether this sphincter-sparing method could produce acceptable morbidity and recurrence rates. METHODS: Patients with rectal cancer 4 to 8 cm from the dentate line underwent laparoscopically-assisted transsacral resection (LTR) with primary anastomosis. With this technique, the rectosigmoid is mobilized via laparoscopy while the patient is in the supine position. Next, the patient is placed in the prone jackknife position, and a segment of rectum is resected by a transsacral approach. Age, estimated blood loss, length of time in the operating room, length of stay, and postoperative complications were noted. Aspects of the tumor pathology regarding stage, lymph nodes, tumor size, and presence of tumor at resection margins also were recorded. RESULTS: A total of 13 patients, ages 26 to 70 years (mean, 52.5 years), underwent the procedure. No perioperative deaths occurred. The mean hospital stay was 9.6 days. The average size of the rectal lesion was 4.3 cm in the largest dimension. The average specimen contained 11.5 total, and 2.0 metastatic lymph nodes. Postoperative complications included two anastomotic breakdowns and two other wound complications. Late follow-up evaluation ranged from 10 to 30 months, with 11 of 13 patients alive (85% survival). Two local recurrences and three distant recurrences were noted at long-term follow-up assessment. CONCLUSIONS: In selected patients with low or midlevel rectal cancer, LTR may be a viable option. Further experience is necessary to define its oncologic efficacy and whether routine temporary diverting colostomy is indicated.

Title

The Syndromes of Sotos and Weaver: Reports and Review.

Date

June 1999

Journal

American Journal of Medical Genetics

Excerpt

The syndromes of Sotos and Weaver are paradigmatic of the daily nosologic difficulties faced by clinical geneticists attempting to diagnose and counsel, and to give accurate prognoses in cases of extensive phenotypic overlap between molecularly undefined entities. Vertebrate development is constrained into only very few final or common developmental paths; therefore, no developmental anomaly seen in humans is unique to ("pathognomonic" of) one syndrome. Thus, it is not surprising that prenatal overgrowth occurs in several syndromes, including the Sotos and Weaver syndromes. Are they sufficiently different in other respects to allow the postulation of locus (rather than allele) heterogeneity? Phenotypic data in both conditions are biased because of ascertainment of propositi, and the apparent differences between them may be entirely artificial as they were between the G and BBB syndromes. On the other hand, the Sotos syndrome may be a cancer syndrome, the Weaver syndrome not (though a neuroblastoma was reported in the latter); in the former there is also remarkably advanced dental maturation rarely commented on in the latter. In Weaver syndrome there are more conspicuous contractures and a facial appearance that experts find convincingly different from that of Sotos individuals. Nevertheless, the hypothesis of locus heterogeneity is testable; at the moment we are inclined to favor the hypothesis of allele heterogeneity. An international effort is required to map, isolate, and sequence the causal gene or genes.

Title

Pseudocysts and Pseudoaneurysms: Surgical Strategy.

Date

May 1995

Journal

Pancreas

Excerpt

Eight patients over an 8-year period required operation for spontaneous hemorrhage as a complication of a pancreatic pseudocyst. Three patients presented with abdominal pain or jaundice and bled in hospital while undergoing work-up. Four patients were admitted with upper gastrointestinal bleeding and one with intraperitoneal bleeding. Five patients were managed by pancreatic resection (two of the head and three of the tail) and three were managed by arterial ligation and internal drainage. There was one death (mortality rate, 12.5%). The first four patients in the series had their operations delayed secondary to a perceived need for further work-up or an inability to make an exact diagnosis of the bleeding site. All rebled, necessitating an emergency operation. The last four patients underwent an expedited workup and operation. Successful treatment of bleeding pancreatic pseudocysts requires good surgical judgment, especially when nonoperative methods fail or aren't applicable. The risk of recurrent hemorrhage is high, suggesting the need for immediate intervention once the diagnosis is made. Resection provides definitive control, although selected patients with easily accessible vessels may be managed more conservatively with ligation and drainage.

We have adopted a uniform, aggressive approach to the management of upper gastrointestinal hemorrhage. Our protocol consists of admission to a surgical service, endoscopy within 24 hours, and liberal use of intensive care monitoring. Urgent or emergency surgery is recommended for the following criteria: 1) presence of shock upon admission; 2) resuscitation requirements of greater than 4 units of blood; 3) age 65 years or older; 4) ulcer size greater than 2 cm or with stigmata of recent hemorrhage; or 5) history of a previous admission for an ulcer complication. During the period 1986-1990, 66 patients met the criteria for operation. There were 45 males and 21 females with an average age of 53.5 years (range, 29-84). Thirty-seven bled from a gastric ulcer and 29 from a duodenal ulcer. They were transfused an average of 5.0 units of blood (range, 0-13). There were no hospital deaths, but 11 patients (16.7%) had 12 postoperative complications. We conclude that a unified, single team approach to gastroduodenal hemorrhage with expedited work-up and early operation prevents death from this treatable condition.

Title

Differential Diagnosis and Management of Unexplained Bleeding.

Date

April 1993

Journal

The Surgical Clinics of North America

Excerpt

A brief overview of normal hemostasis is reviewed. Congenital and acquired causes of bleeding are discussed. Methods for evaluation of the coagulation system of the patient prior to an operative procedure are outlined. A strategy for characterizing intraoperative bleeding disorders and appropriate interventions are discussed.

Title

Alternatives in the Surgical Management of in Situ Breast Cancer. A Meta-analysis of Outcome.

Date

August 1990

Journal

The American Surgeon

Excerpt

The surgical management of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) remains controversial. For in situ breast cancer local excision (LE), local excision and radiation therapy (LERT) and mastectomy (MAST) have all been advocated. A search of the English literature found 13 reports concerning the surgical management of LCIS and 12 reports concerning the management of DCIS. The data were combined in a meta-analysis of outcome. As expected, recurrence rates following LE with both LCIS 8.4%) and DCIS (17%) are high. However,the overall mortality following mastectomy for recurrence, LCIS (2.8%) and DCIS (2.3%) does not differ statistically from those treated initially with mastectomy for LCIS (0.9%) and DCIS (1.7%). We conclude from these data that local recurrence after breast conserving procedures for in situ breast cancer does not carry an ominous prognosis. This knowledge should aid in planning individual therapy.

Title

Percutaneous Denver Peritoneovenous Shunt Insertion.

Date

July 1990

Journal

American Journal of Surgery

Excerpt

A simplified technique for insertion of a peritoneovenous shunt is described. By using a "peel-away" sheath at both ends of the shunt, the insertion is much quicker and less traumatic to the patient.

Title

The Impact of Technology on the Management of Pancreatic Pseudocyst. Fifth Annual Samuel Jason Mixter Lecture.

Date

July 1990

Journal

Archives of Surgery (chicago, Ill. : 1960)

Excerpt

The records of 299 patients with 357 admissions for pancreatic pseudocysts seen between 1960 and 1989 were studied; 233 patients underwent operation. The natural history of pancreatic pseudocysts has been clarified by newer technology, such as ultrasonography, computer tomography, amylase isoenzyme measurements, and endoscopic retrograde cholangiopancreatography. All have influenced diagnosis, nonoperative management, and surgical operation. Differences between pancreatic pseudocysts associated with acute pancreatitis in contrast with chronic pancreatitis, and the complications of obstruction, hemorrhage, rupture, pancreatic ascites, infection, and jaundice can now be more rationally treated. Pancreatic pseudocysts and pancreatic ductal changes are now revealed earlier, especially by endoscopic retrograde cholangiopancreatography. Paradoxically, this information has encouraged nonoperative conservative therapy and also larger operations, eg, resection and adjunctive pancreaticojejunostomy. Partial resection of the pancreas together with the pancreatic pseudocysts was performed in 58 (25%) of the 233 patients. Recent technology permits cautious exploration of selective pancreatic pseudocyst drainage percutaneously or transgastroduodenally avoiding laparotomy.

Title

A Community Survey of the Potential Use of Thrombolytic Agents for Acute Myocardial Infarction.

Date

August 1989

Journal

Annals of Emergency Medicine

Excerpt

We surveyed all patients admitted to nine community hospital coronary care units to determine what proportion could be candidates for thrombolytic therapy. During the 12-month study period, there were 4,115 admissions for possible acute myocardial infarction, and 1,076 (26%) had a discharge diagnosis of myocardial infarction. Patients with myocardial infarction had the following characteristics: 60% had ST elevation seen on the first ECG, 17% had ST depression without ST elevation, 75% were less than 75 years old, 75% had no contraindications to thrombolytic therapy, 78% arrived at hospital within six hours of onset of symptoms, and 94% arrived within 24 hours of symptoms. Criteria for administration of thrombolytic therapy can be grouped as restrictive (arrival within six hours of symptoms and ST elevation) or liberal (arrival within 24 hours of symptoms and ST elevation or ST depression). Applying these characteristics, 26% met restrictive criteria for treatment with thrombolytic therapy, and 36% met liberal criteria. Until liberal criteria (therapy up to 24 hours and ST depression) are convincingly shown to be of benefit, we believe clinicians should apply restrictive criteria to potential candidates for thrombolytic therapy.

Title

Peritoneovenous Shunt (pvs) for Malignant Ascites. An Analysis of Outcome.

Date

August 1989

Journal

The American Surgeon

Excerpt

Fifty cases of malignant ascites were studied to determine what factors influenced outcome after peritoneovenous shunt. There were 36 women and 14 men. The five most common tumor types were colon, breast, gastric, pancreatic, and unspecified adenocarcinoma. Multivariate analysis between those patients surviving longer than 7 weeks (n = 20) and those who died in less than 7 weeks (n = 30) showed that women did uniformly better than men, even excluding the "female malignancies" (P less than 0.01). An elevated white blood cell count (WBC) and low platelets also were strong predictors of poor outcome (P less than 0.5 for difference in means between the two groups). Patients with pancreatic cancer and ascites fared poorly (80% mortality by 7 weeks) as did those with colon cancer (73% mortality by 7 weeks). By contrast, 50 per cent of the patients with breast and gastric cancer lived more than 7 weeks. Twelve patients had a LaVeen shunt placed, compared with 38 who had a Denver shunt. Fifty per cent of the La Veen shunts failed, with a mean time to failure of 69 days (P less than 0.01). Shunt failure, however, had no influence on overall survival.

Early reports support the percutaneous endoscopic gastrostomy (PEG) as an alternative to traditional gastrostomy with lower cost, greater ease of placement, and low morbidity and mortality. The authors' bias has been to attempt PEG on nearly all patients referred to gastrostomy tube prior to performing open gastrostomy. In this light, we reviewed our 32 month experience of 115 PEG placements in 112 adult patients, with a mean follow-up of 59.4 days. Placement was unsuccessful in ten per cent of patients and difficult in another six per cent. Minor postoperative complications not requiring intervention occurred in 9.5 per cent of patients, and major complications in 20 per cent. Infection was the most common postoperative problem. Thirty day mortality was 24 per cent. No patient died as a direct result of the procedure. The ten per cent failure rate is a consequence of attempting PEG as the initial procedure in greater than 90 per cent of patients. PEG can be employed as an initial procedure in even the sickest of patients with a high rate of success, and morbidity comparable to open gastrostomy. This knowledge allows early PEG placement in all types of patients, thereby facilitating their transfer to a non-acute care environment.

Title

Colon Cancer: Surgical Therapy.

Date

April 1989

Journal

Gastroenterology Clinics of North America

Excerpt

Successful treatment of colon cancer is founded on surgical resection of the primary lesion and the regional lymph nodes. The significant number of patients so resected who experience no recurrence, even with positive lymph nodes, indicates that the disease still was confined regionally and that the therapy was effective. Cancer in about 50 per cent of patients does recur, however, and, outside of a small proportion who can be resected again, all patients with recurrence die. There is virtually no curative nonsurgical therapy for colorectal carcinoma.

Title

Surgical Management of Pseudomembranous Colitis.

Date

July 1988

Journal

The American Surgeon

Excerpt

The authors recently studied two cases of pseudomembranous colitis (PMC) that required surgery and combined them with previously reported cases in the literature, which required surgery to propose guidelines for the surgical management of PMC. A total of 21 patients were studied. Indications for surgery included refractory disease in seven patients, toxic megacolon in 12 patients, and perforation in two patients. Operative management ranged from decompressive cecostomy to total proctocolectomy. The best results were obtained with subtotal colectomy and ileostomy. It is concluded that PMC should be managed surgically in a manner analogous to ulcerative colitis. If there is no improvement after 7 days of aggressive medical management, surgical intervention, ileostomy with subtotal colectomy is indicated to prevent complications. Complications of PMC, toxic megacolon and perforation, should also be managed with ileostomy and subtotal colectomy as simple decompression or segmental resection does nothing to alter the underlying disease process.

Title

Learning to Dictate and Report: a Case Study of Operative Report Evolution During Residency Training.

Date

June 1988

Journal

Topics in Health Record Management

Title

Gastrojejunostomy: is It Helpful for Patients with Pancreatic Cancer?

Date

October 1987

Journal

Surgery

Excerpt

A retrospective review of palliative outcome of gastrojejunostomy in patients with pancreatic cancer was conducted. Eighty-one patients were analyzed in two groups depending on duodenal patency. Forty-five patients (group I) had no evidence of duodenal obstruction. Thirty-six patients (group II) had evidence of impingement on the duodenum by the pancreatic cancer. A third subset of patients was also studied for outcome. These 21 patients (five group I and 16 group II) had nausea and vomiting as major symptoms and were judged to have the most to gain from gastrojejunostomy. Patients were categorized by outcome. Poor outcome was defined as either death during the hospitalization for gastrojejunostomy or death within 30 days of operation even if the patient left the hospital. Risk for poor outcome depended on group. In group I, 18 of 45 patients (40%) had a poor outcome compared with 25 of 36 (70%) patients in group II (p less than 0.001). Nineteen of the 21 (90%) patients with nausea and vomiting had a poor outcome. It is an unfortunate paradox that the more patients need gastrojejunostomy for pancreatic cancer, the less likely they are to have a favorable outcome. Gastric outlet obstruction in pancreatic cancer appears to be a terminal event. A prospective study is needed to see if any true palliation of vomiting can be affected in these patients.

Title

Analysis of Hyperamylasemia in Patients with Severe Head Injury.

Date

October 1987

Journal

The Journal of Surgical Research

Excerpt

To evaluate the influence of severe head injury (SHI) on amylase activity, we studied the amylase profile of 60 patients with SHIs and Glasgow Coma Scores less than 10. Fourteen additional multiple trauma patients without head injuries were studied as a control group. We excluded patients with pancreatic injury and abdominal trauma. Total serum amylase (TA), pancreatic isoamylase (PA), and nonpancreatic isoamylase (NPA) levels were measured on Days 0, 2, 4, 7, and 14 postinjury. Values greater than 2 SD above the normal mean were considered elevated. All SHI patients were comatose; 14 died. In the SHI group, TA increased in 23 patients, PA increased in 40, and NPA increased in 14. The source of hyperamylasemia was PA in 14, NPA in one, and mixed in 8 patients. While PA increases occurred throughout the study, NPA elevations occurred early. These increases did not correlate with shock (BP less than 80 mm Hg; 17 patients), facial trauma (24 patients), or associated injury (29 patients). On Day 7 postinjury, the mean TA (215 du%) and the mean PA (203.8 du%) were significantly elevated in the SHI patients compared to controls (122.1 du%, P less than 0.05, Wilcoxon's rank sum test). These data indicate that serum amylase is not a reliable index of pancreatic injury in patients with SHI. Severe head injury and multiple trauma activate pathways that increase amylase levels in the blood, suggesting a central nervous system regulation of serum amylase levels.

Preoperative screening chest x-ray studies continue to be used widely despite the high cost and reported low-yield. Most physicians now use "clinical judgment" to mitigate the frequency of chest x-ray. To determine the usefulness of "selective" preoperative chest x-ray studies, 403 consecutive patients undergoing operation were prospectively studied. Chest x-ray films were analyzed both for abnormality and the frequency with which the changes seen on x-ray films led to cancellation of surgery or resulted in a further evaluation of the pathology discovered. There were 228 male and 175 female patients, (average age: 54 years). A total of 166 (41%) patients had operations performed without a preoperative chest x-ray study. The x-ray studies on 136 of the 237 patients who had preoperative chest x-ray were considered normal. A variety of abnormalities such as effusion, cardiomegaly, atelectasis, or granuloma were found in the remaining 101 patients. Sixty-four of these patients were known from previous studies to have the abnormality that was recorded. Eight of 37 (21%), who had surgery as scheduled, subsequently underwent evaluation for the new pulmonary problem detected on x-ray films. Only two operations were cancelled as a result of the screening x-ray. The majority of abnormalities detected were already known or were considered insufficient for further evaluation. In a metropolitan area of Michigan the cost for a chest x-ray is $70. Projected nationwide, more than $1 billion could be saved on needless "selective" preoperative chest x-ray studies each year. These data suggest that preoperative chest x-ray is still widely overused.(ABSTRACT TRUNCATED AT 250 WORDS)

Title

Intestinal Obstruction in Cancer Patients. An Assessment of Risk Factors and Outcome.

Date

August 1986

Journal

The American Surgeon

Excerpt

Eighty-four patients with a total of 104 admissions for intestinal obstruction who each also had a history of cancer had their records reviewed to determine what variables, if any, would help predict outcome. Multivariate discriminate analysis was used to assign the patient into one of three outcome possibilities: 1) alive and well, 2) alive with intestinal obstruction, and 3) dead. The computer accurately assigned outcome 71 per cent of the time. Twenty-four per cent of the patients had no cancer found at laparotomy, and had good results. Patients with carcinomatosis did poorly. Females fared much better than males. The natural history of patients with intestinal obstruction and cancer is that about 35 per cent leave the hospital eating normally, 20 per cent are alive but unable to eat, and 45 per cent die on the same hospital admission or shortly thereafter.

Seven of 26 patients undergoing insertion of "Infusaid" perfusion pumps with hepatic artery catheters for regional hepatic perfusion with 5 fluorodeoxyuridine were diagnosed to have gastritis (n = 5) or penetrating duodenal ulcers with catheter exposure (n = 2). Diagnosis is best achieved by esophagogastroduodenoscopy. The ulcers required removal of the pumps and gastric resections. The gastritis responded only to cessation of drug infusion. These complications represent a significant risk to regional hepatic chemotherapy. Physicians caring for this group of patients will be unable to predict which individuals will suffer these complications when using preoperative or postoperative parameters such as age, sex, tumor type, arterial anatomy or flow patterns on nuclear isotope scanning. A high index of suspicion must be maintained during the critical third and fourth cycles of chemotherapy in all patients undergoing regional hepatic chemotherapy.

Title

Serum Amylase Levels: Evidence for Homeostatic Control.

Date

September 1985

Journal

Current Surgery

Title

Interpretation of Serum Amylase Levels in the Critically Ill Patient.

Date

August 1985

Journal

Critical Care Medicine

Excerpt

To understand better the incidence and meaning of hyperamylasemia in the intensive care setting, cellulose acetate membrane electrophoresis was used to measure the isoenzymes of serum amylase in 192 patients with a variety of critical illnesses. Seventy of these patients had elevated serum amylase levels, but none had clinical or biochemical evidence of acute pancreatitis or renal failure. Of the 70 patients who had hyperamylasemia, in only 18 (26%) was it due solely to an elevation of the pancreatic isoamylase fraction. The remaining 52 patients were hyperamylasemic due to elevations in the nonpancreatic isoamylase fraction or elevations in both pancreatic and nonpancreatic isoamylase fractions. These data indicate that hyperamylasemia in the absence of clinical pancreatic disease is common in the ICU and is frequently caused by nonpancreatic production of serum amylase. Caution is, therefore, advised in interpreting elevated serum amylase levels in critically ill patients.

Title

The Poor Man's Isoamylase Analysis (wheat Inhibitor). Does It Work?

Date

June 1985

Journal

The American Surgeon

Excerpt

The value of a wheat inhibitor assay to measure the pancreatic isoamylase fraction in the serum was evaluated in a clinical trial. Fifty-four patients with a variety of disorders and wide range in serum amylase levels were studied comparing pancreatic isoamylase levels measured by both cellulose acetate membrane electrophoresis and wheat inhibitor assay. The overall correlation was excellent (r = 0.96), and was best when the total serum amylase was high. The predominate serum isoamylase was correctly predicted in 45 of 54 (83%) patients, with an overall specificity of 73 per cent and sensitivity of 96 per cent. Because it is easy to perform, the test is recommended for clinical use by those without access to more sophisticated forms of isoamylase analysis.

The isoamylase profile in 24 patients undergoing ERCP were prospectively studied. Serum samples were obtained prior to and 4 hours following ERCP. All patients had the bile duct successfully visualized and in all but one patient the pancreatic duct was seen. Twenty-two of the 24 patients had a rise in the total serum amylase following ERCP. Most often this was from pancreatic sources, but two patients had a substantial rise in the salivary isoamylase. No patient developed clinical signs of acute pancreatitis. The patients in whom ductal pathology was found had a significant rise in pancreatic isoamylase following ERCP. Patients with normal pancreatic ducts did not show a significant rise in the pancreatic isoamylase. Patients who were hyperamylasemic prior to ERCP had a statistically significant post-ERCP rise in pancreatic isoamylase. In contrast, those who were normoamylasemic had no significant change in their pancreatic isoamylase level following the procedure. Development of hyperamylasemia is an expected sequela of ERCP, most often is due to pancreatic sources, and is rarely of clinical significance.

Title

Serum Amylase and Its Isoenzymes: a Clarification of Their Implications in Trauma.

Date

September 1984

Journal

The Journal of Trauma

Excerpt

Previous reports on the use of the serum amylase level to assess pancreatic injury in patients with blunt abdominal trauma have been disappointing. The availability of methods to measure the serum isoamylases (P & NP) might be expected to improve the accuracy with which the serum amylase level is used. Sixty-one patients treated for a variety of blunt trauma injuries were studied. All categories of injury were included. Isoamylase levels were determined from admission sera and were compared to injuries found at laparotomy. Three patients had major pancreatic injury but only two of these patients showed a rise in the pancreatic isoamylase. Sixteen additional patients had a rise in the pancreatic isoamylase without evidence of pancreatic injury. Eight of these patients had no component of abdominal injury whatsoever. Two patients with isolated head injury had substantial elevations of pancreatic isoamylase. The regulation of serum amylase is multifactorial and variable. The measurement of serum isoamylase levels does not offer great improvement over the serum amylase in evaluating patients with blunt abdominal trauma.

Title

Outcome After Peritoneo-jugular Shunting of Pancreatic Ascites.

Date

August 1984

Journal

The American Surgeon

Excerpt

Three patients with pancreatic ascites documented by ascitic fluid protein greater than 2.5 g/dl and elevated amylase in their peritoneal fluid were treated by peritoneo-jugular shunting (PJS). Patient 1 was so treated inadvertently; Patient 2 had resolving amylase levels but increasing amounts of ascites; Patient 3 had clear, active pancreatic ascites. None incurred untoward effects from this procedure. Ventilatory compromise from reduced diaphragmatic excursion was ameliorated in all patients. Two patients required no further therapy. The third patient was greatly improved in preparation for definitive surgical therapy for a leaking pancreatic pseudocyst. The infusion of enzyme-rich fluids into the circulation may be responsible for certain systemic effects of pancreatitis. Coagulation defects are a known complication of PJS for the ascites of Laennec's cirrhosis. There was no evidence of histamine-mediated cardiovascular collapse, exacerbation of respiratory failure, or coagulation defects in these patients. We conclude that these complications are not the inevitable results of PJS of pancreatic ascites.

Title

Hyperamylasemia After Cardiopulmonary Bypass.

Date

July 1984

Journal

The American Surgeon

Excerpt

Postpump pancreatitis has been described to occur in patients undergoing cardiac surgery with cardiopulmonary bypass. Twenty patients were prospectively analyzed with sera drawn for total serum amylase, pancreatic isoamylase, and nonpancreatic isoamylase levels. Six of 19 patients were found to be hyperamylasemic postoperatively, the majority of which were not due to pancreatic isoamylasemia . No patient had clinical pancreatitis. These findings suggest that elevations of serum amylase is common after cardiopulmonary bypass and is not indicative of pancreatitis.

Title

Alcohol-induced Salivary Hyperamylasemia.

Date

May 1984

Journal

The Journal of Surgical Research

Excerpt

The effects of alcohol intoxication on serum amylase levels were tested in both normal subjects and chronic alcoholics. Paired samples of ethanol levels and isoamylase levels in the normal subjects (n = 11) showed a rise in both total serum amylase (P less than 0.01) and nonpancreatic isoamylase (P less than 0.05) after drinking. Unpaired cohort groups of sober chronic alcoholics at a rehabilitation facility (n = 46) and intoxicated chronic alcoholics in an emergency room (n = 58) were also compared. Average blood alcohol levels in the intoxicated controls were 93 mg% compared to a level of 301 mg% in the intoxicated chronic alcoholic. Intoxication superimposed on chronic alcoholism caused a moderate rise in the total serum amylase (NS) and a significant elevation of the nonpancreatic isoamylase (P less than 0.01). Sober chronic alcoholics had a significantly greater average total serum amylase (P less than 0.001) and nonpancreatic isoamylase (P less than 0.01) than the normal controls. No difference in the average pancreatic isoamylase levels was seen in any group. These data suggest a biphasic response to alcohol on the serum amylase level. Acute and chronic changes appear to operate independently. The cause for these effects is speculative. Isoamylase analysis is needed in the alcoholic population to sort out the meaning of hyperamylasemia.

Title

Acute Alcohol Intoxication: Significance of the Amylase Level.

Date

November 1983

Journal

Annals of Emergency Medicine

Excerpt

To evaluate the effects of acute alcohol intoxication on serum amylase and isoamylase levels, 58 clinically intoxicated patients with blood alcohol levels greater than 100 mg/dL were studied. Comparisons were made to normal control and a sober chronic alcoholic group. Admitting serum isoamylase levels were determined by cellulose acetate membrane electrophoresis and serum amylase levels measured by the Amylochrome technique. The average blood alcohol level in the intoxicated group was 301 +/- 99 mg/dL. Thirty of the 58 patients had hyperamylasemia (greater than 207 IU). Twenty-five of these 30 patients had hyperamylasemia from nonpancreatic sources (increased salivary isoamylase). Two of the 30 patients had pancreatic hyperamylasemia and three patients had elevated levels of both isoamylases. Neither of the patients with pancreatic hyperamylasemia had clinical evidence of acute pancreatitis. Although nine of the 58 patients had abdominal pain and clinical symptoms suggestive of acute pancreatitis, none of these patients had elevated pancreatic isoamylase. The finding of hyperamylasemia in acutely intoxicated patients is common. This is most frequently due to a rise in the salivary (nonpancreatic) isoamylase. The reliability of the total serum amylase as an indication of pancreatic disease in the intoxicated patient is questioned.

Title

Hyperamylasemia: a Result of Intracranial Bleeding.

Date

September 1983

Journal

Surgery

Excerpt

The unexpected finding of hyperamylasemia in a patient with isolated head injury prompted a study of amylase levels in patients with various degrees of cranial trauma. None of seven patients with isolated maxillofacial trauma had hyperamylasemia. This group was studied to discount injury to salivary glands as a source of elevated amylase levels. Only one of ten patients with simple cranial injury without computerized tomographic (CT) scan evidence of intracranial bleeding had hyperamylasemia. Six of ten patients with CT scans positive for intracranial bleeding had hyperamylasemia. Isoamylase analysis showed that the source of the hyperamylasemia was varied. These results suggest a central neural control of serum amylase levels. The reliability of the serum amylase level as an indication of pancreatic trauma in a patient with concomitant head injury is questioned.

Title

Foregut Mucosal Defects: an Etiology of Hyperamylasemia.

Date

July 1983

Journal

The Journal of Surgical Research

Excerpt

To evaluate a preliminary correlation of hyperamylasemia to upper gastrointestinal bleeding, total serum amylase and serum isoamylase profiles were determined in 50 patients with upper gastrointestinal bleeding. Etiologies of the bleeding were determined in 46 patients including gastritis or duodenitis in 25, gastric ulcers in 12, duodenal ulcers in 3, Mallory-Weiss tears in 3, gastric carcinoma in 2, and esophageal varices in 1. Gastritis or duodenitis was seen incidentally in 14 more patients. Hyperamylasemia was seen in 38 patients, most commonly being due to a rise of both nonpancreatic and pancreatic isoamylases (18 patients). In 13 patients it was due to an elevation of nonpancreatic amylase alone, and in 7 patients secondary to elevated pancreatic isoamylase alone. Acute pancreatitis raises only the pancreatic component and cannot explain the hyperamylasemia in most of these patients. Hyperamylasemia did not correlate to etiology of the bleeding; gastritis or duodenitis present in the majority of these patients appears to be the unifying factor. Since both nonpancreatic and pancreatic amylases are present in the duodenum and the stomach with pyloric reflux, reabsorption of intraluminal amylase across damaged mucosa is postulated as a mechanism to explain the observed isoamylase patterns. The possibility of decreased amylase clearance as an explanation is unlikely. An alternative central nervous system mechanism might be invoked. It is concluded that hyperamylasemia is a complex event which the use of isoamylase analysis is beginning to elucidate. The hyperamylasemia seen commonly in patients presenting with upper gastrointestinal bleeding does not imply the presence of acute pancreatitis.

Title

A Correlation Between Clinical Pancreatitis and Isoenzyme Patterns of Amylase.

Date

December 1982

Journal

Surgery

Excerpt

Fifty-seven patients admitted with the clinical diagnosis of acute pancreatitis had isoamylase analysis on their sera to determine the source of their hyperamylasemia. Our objective was to correlate the isoamylase pattern with our clinical observations. Thirty-nine of 57 patients (68%) had pancreatic hyperamylasemia as expected, but 18 of 57 patients (32%) had normal levels of pancreatic amylase. The hyperamylasemia in the latter group was due either to nonpancreatic hyperamylasemia (16 of 57) of macroamylasemia (2 of 57). Consequently, hyperamylasemia associated with abdominal pain, nausea, and vomiting led to the incorrect diagnosis of acute pancreatitis in 32% of the patients. The measurement of isoamylase profiles can be done rapidly and inexpensively. Knowledge that hyperamylasemia is nonpancreatic in origin may have an important influence on treatment, hospitalization, and the extent of laboratory and radiologic investigation.

Title

A Continuing Appraisal of Pancreatic Ascites.

Date

July 1982

Journal

Surgery, Gynecology & Obstetrics

Excerpt

Pancreatic ascites is a distinct clinical entity characterized by elevated amylase and protein levels in the ascitic fluid. This should be distinguished from the ascites of cirrhosis, tuberculosis or metastatic carcinoma. Precise delineation of the ductal anatomy by endoscopic retrograde pancreatography preoperatively will enhance the ability of the surgeon to plan a rational operation and will, thereby, provide the best results. Medical treatment may obviate surgical intervention in a small number of instances but contains intrinsic hazards and should not be prolonged beyond three weeks. In carefully selected patients, limited pancreatic resection, encompassing the site of leakage, produces excellent results.

Amylase-rich fluid that incubates ("ages") within a pancreatic pseudocyst undergoes a change that can be detected by isoenzyme analysis of amylase from the serum. This aging is a result of deamination of the asparagine and glutamine residues on the amylase molecule. Eighteen of 20 patients with surgically proved pseudocysts had greater than 15% aged (deaminated) amylase in their serum. Levels of aged amylase returned to normal following treatment of their pseudocysts. Twenty of 23 patients with acute pancreatitis had levels of aged amylase below 15% (P less than .05). A criterion of 15% aged amylase resulted in 87% specificity, and 91% sensitivity for the diagnosis of pseudocysts. Because this test is noninvasive and easy to perform, it should become the ideal screen for patients at risk of development of pseudocysts, Endoscopic retrograde pancreatography, ultrasonography, and abdominal computed tomographic scanning should be reserved for confirmation of the diagnosis when the result of isoenzyme analysis is positive.

Title

Impaired Pulmonary Function After Albumin Resuscitation from Shock.

Date

July 1980

Journal

The Journal of Trauma

Title

Effects of Albumin on Serum Protein Homeostasis After Hypovolemic Shock.

The effect of albumin when added to the resuscitation regimen of patients in hypovolemic shock was studied in a randomized prospective manner in 52 injured patients who received an average of 15.3 transfusions, 9.6 liters of balanced electrolyte solution, and 980 ml of fresh frozen plasma. Before and during operation, 27 patients received an average of 25 gm of albumin and 150 gm/day for three to five days. Patients who received albumin had greater dependence on respiratory support, averaging eight days while receiving ventilatory support with volume ventilator compared with three days in patients not receiving albumin. Furthermore, patients receiving albumin had forced inspiratory oxygen/Pao2 ratios that were statistically and significantly higher than those of patients not receiving albumin during all phases of their hospital course. These effects were associated with increased plasma volumes caused by the oncotic effects of albumin and by its interference with saline diuresis. On the basis of this preliminary report, albumin seems to have a detrimental effect on respiratory function.

Title

The Number of Lymph Nodes Identified in a Simple Pancreatoduodenectomy Specimen: Comparison of Conventional Vs Orange-peeling Approach in Pathologic Assessment.

Date

Journal

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc

Excerpt

Lymph node status is one of the most important predictors of survival in resectable pancreatic ductal adenocarcinoma; therefore, thorough lymph node evaluation is a critical assessment in pancreatoduodenectomy specimens. There is considerable variability in pancreatoduodenectomy specimens processed histologically. This study compares two approaches of lymph node dissection and evaluation (standard vs orange peeling) of pancreatoduodenectomy specimens. A different approach to dissection of pancreatoduodenectomy specimens was designed to optimize lymph node harvesting: All peripancreatic soft tissues were removed in an orange-peeling manner before further dissection of the pancreatic head. This approach was applied to 52 consecutive pancreatoduodenectomy specimens performed for ductal adenocarcinoma at two institutions. Specimen dissection was otherwise performed routinely. Overall number of lymph nodes harvested, number of positive lymph nodes, and their anatomic distribution were analyzed and compared with cases that had been dissected by the conventional approach. The mean number of lymph nodes identified by the orange-peeling approach was 14.1 (by institution, 13.8 and 14.4), as opposed to 6.1 (by institution, 7 and 5.3) in cases processed by conventional approach (P=0.0001). The number of lymph node-positive cases also increased substantially from 50% (by institution, 54 and 46%) in the conventional method to 73% (by institution, 88 and 58%) in the orange-peeling method (P=0.02). The orange-peeling method of lymph node harvest in pancreatoduodenectomy specimens for ductal adenocarcinoma enhances overall and positive lymph node yield and optimizes ductal adenocarcinoma staging. Therefore, lymph node harvest by the orange-peeling method should be performed routinely before specimen sectioning in assessment of pancreatoduodenectomy for ductal adenocarcinoma.Modern Pathology advance online publication, 26 September 2008; doi:10.1038/modpathol.2008.167.

Title

Anticancer Activity of a Broccoli Derivative, Sulforaphane, in Barrett Adenocarcinoma: Potential Use in Chemoprevention and As Adjuvant in Chemotherapy.

Date

Journal

Translational Oncology

Excerpt

The incidence of Barrett esophageal adenocarcinoma (BEAC) has been increasing at an alarming rate in western countries. In this study, we have evaluated the therapeutic potential of sulforaphane (SFN), an antioxidant derived from broccoli, in BEAC.

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